This study seeks to determine in two inbred strains of mice, BALB/ cJ and CBA/J the cellular and biochemical mechanisms accounting for the strain-dependent variations in spontaneous behavior and responses to psychoactive drugs which depend upon the integrity of central dopaminergic (DA) neurons. Its aims will be to determine: (a) whether the strain dependent variations in brain tyrosine hydroxylase (TH) activity occur in all central DA systems; (b) if the differences in enzyme activity in all regions are due to variations in amount of enzyme protein, in turn, (c) a consequence of variations in the numbers of DA containing neurons (as measured by immunocytochemical staining for TH). It will also seek to assess (d) if such variability is associated with variations in size and neuronal numbers of two target organs of DA neurons, the caudate nucleus of olfactory turbercle, and to assess (e) if these targets share the same number of constituent neurotransmitters and receptors. It will also seek to determine (f) whether the number of dopaminergic neurons correlates with the behavioral responses (motility and exploratory activity) to DA agonists and antagonists (d-amphetamine, apomorphine and chlorpromazine) and also behaviors dependent on the integrity of the DA system (motility and exploration). (g) Cross-breeding and backbreeding studies will be undertaken to assess if all traits segregate together and to determine the mode of inheritance of these traits and to assess thereby if it is under single gene control.